Nasal trigeminal chemosensitivity in mice and rats is mediated in part by solitary chemoreceptor cells (SCCs) in the nasal epithelium. SCCs express the G-protein a-gustducin in addition to other elements of the "bitter"- taste signaling cascade including PLCp2, TrpM5 and T2R "bitter"-taste receptors. Many noxious substances elicit the sensation of bitter taste in the oral cavity but are irritating or painful in the nasal cavity. The proposed experiments fall into 2 aims: first to describe what type of trigeminal nociceptive fibers innervate SCCs. We will utilize immunocytochemistry to assay nerve fibers innervating SCCs for neuropeptide content, the ability to bind isolectin B4, and the expression of P2X3 and kainate receptors, both of which are commonly expressed by nociceptive fibers. Second, we will investigate which part of the SCC response is TrpM5-mediated. TrpMS is an obligatory component of T2R-mediated responses in taste cells and TrpM5- KO mice lack taste responses to T2R ligands. We will use calcium imaging to visualize SCC responses to test stimuli from a panel of classic bitter and trigeminal stimuli. Responses will be recorded in SCCs from both wild type and TrpM5-KO mice to separate TrpM5 and non-TrpM5-mediated responses. [unreadable] [unreadable] [unreadable]